Abstract
Neuropsychiatric disorders, which arise from a combination of genetic, epigenetic and environmental influences, epitomize the challenges faced in understanding the mammalian brain. Elucidation and treatment of these diseases will benefit from understanding how specific brain cell types are interconnected and signal in neural circuits. Newly developed neuroengineering tools based on two microbial opsins, channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), enable the investigation of neural circuit function with cell-type-specific, temporally accurate and reversible neuromodulation. These tools could lead to the development of precise neuromodulation technologies for animal models of disease and clinical neuropsychiatry.
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Acknowledgements
We acknowledge the collective effort of the entire Deisseroth laboratory over the years and our many outstanding co-authors, including R.D. Airan, G.J. Augustine, E. Bamberg, E.S. Boyden, M. Ehlers, G. Feng, A. Gottschalk, V. Gradinaru, J. Henderson, L.A. Meltzer, M. Mogri, G. Nagel, M. Roy, M.B. Schneider and L.-P. Wang. We also acknowledge our colleagues and mentors including R. Altman, P.S. Buckmaster, S. Delp, J. Huguenard, R.C. Malenka, S. Quake, M. Scott, R.W. Tsien and P. Yock. F.Z. is supported by a Ruth L. Kirschstein NRSA. A.M.A. is supported by the Walter and Idun Berry Foundation. A.A. is supported by the Belgian American Educational Foundation and the Fondation Leon Fredericq. L.L. is supported by the NIMH and NIDA. K.D. is supported by NARSAD, APIRE and the Snyder, Culpeper, Coulter, Klingenstein, Whitehall, McKnight, and Albert Yu and Mary Bechmann Foundations, as well as by NIMH, NIDA and the NIH Director's Pioneer Award Program. We apologize to those authors whose work we could not cite or discuss due to space limitations. The materials and methods described herein are freely distributed and supported by the authors.
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Glossary
- Deep brain stimulation
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(DBS). A surgical procedure involving the implantation of electrodes to deliver electrical pulses to specific brain regions; used to treat neuropsychiatric disorders such as Parkinson's disease, and currently under evaluation for other disorders, including clinical depression and Tourette's syndrome.
- Retrograde label
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A method used to examine neuronal connectivity in which an injected label travels within neurons in the opposite direction of neural information flow, thereby labelling the cell bodies that project to the injected location. An anterograde label will track axons projecting from the injection site.
- Transcranial magnetic stimulation
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(TMS). A non-invasive method for exciting neurons by inducing electrical currents in the brain with rapidly changing external magnetic fields; currently under evaluation for diagnostic and therapeutic use in diseases, including depression and Parkinson's disease.
- Vagus nerve stimulation
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(VNS). A device-based neural stimulation method that uses an electrical lead to stimulate the vagus nerve in the neck, which may then influence central neurons. It is used to treat intractable epilepsy and has recently been applied to clinical depression.
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Zhang, F., Aravanis, A., Adamantidis, A. et al. Circuit-breakers: optical technologies for probing neural signals and systems. Nat Rev Neurosci 8, 577–581 (2007). https://doi.org/10.1038/nrn2192
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DOI: https://doi.org/10.1038/nrn2192
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